Quinolone type structures are known for their antibacterial properties, and several quinolone antibiotics (e.g. norfloxacin and ciprofloxacin) are on the market. The physical properties of a marketed quinolone are very important. A quinolone with excellent antibiotic properties but which has a shelf life of only a day would be useless. A quinolone with excellent antibiotic properties but which does not dissolve into a useful solvent would be equally useless. Quinolones, when purified, may form crystals or crystal like forms, that can have different shapes and physical properties.
Solids, including pharmaceuticals, often have more than one crystal form and this is known as polymorphism. Polymorphism occurs when a compound crystallizes in a multiplicity of solid phases that differ in crystal packing. Numerous examples are cited in the standard references of solid state properties of pharmaceuticals, Byrn, S. R., Solid-State Chemistry of Drugs, New York, Academic Press (1982); Kuhnert-Brandstatter, M., Thermomiscroscopy In The Analysis of Pharmaceuticals, New York, Pergamon Press (1971) and J. Pharm. Sci., 58, 911 (1969). Byrn states that, in general, polymorphs exhibit different physical characteristics including solubility and physical and chemical stability.
Because of differences in molecular packing, polymorphs may differ in ways that influence drug release, solid-state stability, and pharmaceutical manufacturing. The relative stability and the interconversions of polymorphs are particularly important to the selection of a marketed drug. A suitable polymorph may hinge upon the issue of physical stability. For example, the selection of a marketed drug may depend upon the availability and selection or a suitable polymorph having desirable characteristics, such as excellent physical stability. The performance of the solid dosage form should not be limited by polymorphic transformations during the shelf life of the product. It is important to note that there is no reliable method to predict the observable crystal structures of a given drug or to predict the existence of polymorphs with desirable physical properties.
This invention describes a new form of a quinolone that has physical properties highly desirable for pharmaceutical development.